MR1 presents microbial vitamin B metabolites to MAIT cells

L Kjer-Nielsen, O Patel, AJ Corbett, J Le Nours… - Nature, 2012 - nature.com
L Kjer-Nielsen, O Patel, AJ Corbett, J Le Nours, B Meehan, L Liu, M Bhati, Z Chen…
Nature, 2012nature.com
Antigen-presenting molecules, encoded by the major histocompatibility complex (MHC) and
CD1 family, bind peptide-and lipid-based antigens, respectively, for recognition by T cells.
Mucosal-associated invariant T (MAIT) cells are an abundant population of innate-like T
cells in humans that are activated by an antigen (s) bound to the MHC class I-like molecule
MR1. Although the identity of MR1-restricted antigen (s) is unknown, it is present in
numerous bacteria and yeast. Here we show that the structure and chemistry within the …
Abstract
Antigen-presenting molecules, encoded by the major histocompatibility complex (MHC) and CD1 family, bind peptide- and lipid-based antigens, respectively, for recognition by T cells. Mucosal-associated invariant T (MAIT) cells are an abundant population of innate-like T cells in humans that are activated by an antigen(s) bound to the MHC class I-like molecule MR1. Although the identity of MR1-restricted antigen(s) is unknown, it is present in numerous bacteria and yeast. Here we show that the structure and chemistry within the antigen-binding cleft of MR1 is distinct from the MHC and CD1 families. MR1 is ideally suited to bind ligands originating from vitamin metabolites. The structure of MR1 in complex with 6-formyl pterin, a folic acid (vitamin B9) metabolite, shows the pterin ring sequestered within MR1. Furthermore, we characterize related MR1-restricted vitamin derivatives, originating from the bacterial riboflavin (vitamin B2) biosynthetic pathway, which specifically and potently activate MAIT cells. Accordingly, we show that metabolites of vitamin B represent a class of antigen that are presented by MR1 for MAIT-cell immunosurveillance. As many vitamin biosynthetic pathways are unique to bacteria and yeast, our data suggest that MAIT cells use these metabolites to detect microbial infection.
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